PET in breast cancer
Whole-body PET scanners are not optimal for the evaluation of primary breast cancer, but have been used for the staging of metastatic disease beyond the breast. High-resolution dedicated breast PET scanners offer 1.5-2.0 mm spatial resolution, allowing for reliable detection of even small lesions (García Hernández et al., 2016; O'Connor et al., 2017).
The estrogen receptor (ER) and progesterone receptor (PR) are important biomarkers in the diagnosis, prognosis, and follow-up of the therapeutic response of breast tumours, and specific PET radiopharmaceuticals for these receptors have been developed (Oliveira et al., 2013). Estrogen receptor radioligand Whole-body [18F]FES PET has high diagnostic accuracy in assessing ER status in metastatic breast cancer (van Geel et al., 2022). [18F]4FMFES may offer better tumour contrast than [18F]FES (Paquette et al., 2018). The androgen receptor (AR) is expressed in breast cancer, and steroidal androgens have been used to treat metastatic breast cancer. The effect of selective AR modulators can be assessed using AR radioligands, such as [18F]FDHT (Boers et al., 2021; Jacene et al., 2022).
[18F]FDG is the most used PET tracer for breast cancer imaging, but other tracers could be used as well (Wahl et al., 1993; Fowler, 2014; Lebron et al., 2015; Dalm et al., 2016). [18F]FDG may be useful in staging and detection of metastases in male breast cancer patients, as well (Ulaner et al., 2019). High spleen-to-liver ratio is associated with low stromal tumour-infiltrating lymphocytes (TILs) levels (Seban et al., 2021). Dynamic [18F]FDG PET can provide both K1 and Ki, which predict disease-free survival better than SUV from static imaging (Dunnwald et al., 2011).
Perfusion in breast tumours has been studied using radiowater PET, and the initial uptake rate of other tracers, such as [18F]FDG (Eby et al., 2008; Specht et al., 2010). [18F]fluoride PET can be used to estimate perfusion and fluoride uptake in bone metastases (Doot et al., 2010), but not in primary breast cancer (Sarikaya et al., 2018).
Amino acid tracer [18F]fluciclovine is used for the detection of recurrent prostate cancer, but it has also shown promise in imaging of breast cancer (Ulaner et al., 2018). L-[11C]methionine is also useful for detecting breast cancer (Leskinen-Kallio et al., 1991a; Huovinen et al., 1993).
Gastrin-releasing peptide receptors are overexpressed in breast cancer, and specific PET tracers have been used to detect the tumours.
Fibroblast activation protein (FAP) is expressed on membranes of activated fibroblasts in various carcinomas. [68Ga]FAPI was found to be superior to [18F]FDG in detecting breast cancer lesions (Elboga et al., 2021).
Mutations, amplifications, and fusions of FGFR genes have been observed in tumours. In breast cancer the genetic alterations in FGFR1 and FGFR2 are found especially in treatment resistant tumours, offering a target for new therapies. For instance, an FGFR inhibitor dovitinib dilactic acid decreased tumour growth and [18F]FDG uptake in mice model of human breast cancer (Kähkönen et al., 2019).
Breast cancer and its metastases express PSMA (Wernicke et al., 2014; Nomura et al., 2014), and for example [68Ga]PSMA-11 can be used for PET imaging (Kasoha et al., 2017; Sathekge et al., 2017; Morgenroth et al., 2019).
About 20% of breast cancers overexpress HER2 (ErbB2), and the patients suitable for HER2-targeted therapy can be selected using specific PET radioligands (Keyaerts et al., 2016). Therapeutic inhibition of HER2 can lead to rapid compensatory increase in HER3 (ErbB3). Patients who may benefit from combination of HER2 and HER3 inhibition can be selected using HER3-targeting radioligands, such as [68Ga]HER3P1 (Wehrenberg-Klee et al., 2021).
Altunay B, Morgenroth A, Mottaghy FM. Use of radionuclide-based imaging methods in breast cancer. Semin Nucl Med. 2022; 52: 561-573. doi: 10.1053/j.semnuclmed.2022.04.003.
Bombardieri E, Bonadonna G, Gianni L (eds.): Breast Cancer - Nuclear Medicine in Diagnosis and Therapeutic Options. Springer, 2008. ISBN 978-3-540-36780-2. doi: 10.1007/978-3-540-36781-9.
Miladinova D. Molecular imaging in breast cancer. Nucl Med Mol Imaging 2019; 53(5): 313-319. doi: 10.1007/s13139-019-00614-w.
Piccart MJ, Wood WC, Hung C-M, Solin LJ, Cardoso F (eds.): Breast Cancer and Molecular Medicine. Springer, 2006. ISBN 978-3-540-28265-5. doi: 10.1007/978-3-540-28266-2.
Updated at: 2023-01-08
Created at: 2018-01-09
Written by: Vesa Oikonen